Evidence map›Paper›PMID 29568976›Full record

Trial reportEuropean journal of clinical pharmacology2018

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers.

Arne Kristian Skulberg, Ida Tylleskar, Turid Nilsen, Sissel Skarra, Øyvind Salvesen, Trond Sand, Thorsteinn Loftsson, Ola Dale

2 registry-linked trialsAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02307721 phase1 / phase2completednot on this map

Pharmacokinetics and Pharmacodynamics of a New Formulation of Nasal Naloxone for Prehospital Use

TypeinterventionalSponsorNorwegian University of Science and TechnologyRan2014 to 2015Enrolled12ConditionsDrug OverdoseArmsIntranasal naloxone, Intramuscular naloxone, Remifentanil, Aptar Unidose
NCT04310579 phase1completednot on this mapstarted 2020, after this paper: background citation

Clinical Study to Investigate the Effect of the Combination of Psychotropic Drugs and an Opioid on Ventilation

TypeinterventionalSponsorFood and Drug Administration (FDA)Ran2020 to 2021Enrolled55ConditionsHypercapnia, Ventilatory DepressionArmsOxycodone and Midazolam, Oxycodone, Paroxetine, and Quetiapine
3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Arne Kristian SkulbergDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway.
Ida TylleskarDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway.
Turid NilsenDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway.
Sissel SkarraDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway.
Øyvind SalvesenDepartment of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Trond SandDepartment of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Thorsteinn LoftssonDepartment of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
Ola DaleDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU-Norwegian University of Science and Technology, Post-Box 8905, 7491, Trondheim, Norway. ola.dale@ntnu.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThis study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg.

methodsTwo-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured.

resultsThe relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference.

conclusionsA target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose.

trial registrationclinicaltrials.gov : NCT02307721.

Indexed as

Models, BiologicalAdministration, IntranasalAdultAnalgesics, OpioidCross-Over StudiesFemaleHealthy VolunteersHumansInjections, IntramuscularMaleMiosisNaloxoneNarcotic AntagonistsPainPiperidinesPupilAnalgesics, OpioidNaloxoneNarcotic AntagonistsPiperidinesRemifentanilDrug overdoseIntranasalNaloxonePharmacodynamicsPharmacokineticsRemifentanil

Identifiers

PMID29568976

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.